Abstract Background Dennettia tripetala (Pepperfruit) is an important medicinal plant in some West African communities. This study was designed to examine the antibacterial properties and wound-healing abilities of D. tripetala essential oil on mice with methicillin-resistant Staphylococcus aureus (MRSA) infections. Gas chromatography-mass spectrometry (GC–MS) was used to analyse the essential oil (EO) extracted by hydro-distillation from the dried fruits of D. tripetala. MRSA was identified using 30 µg cefoxitin disk, CHROMagar, and Polymerase Chain Reaction. Congo red agar and tube technique were used to assess the production of biofilms. The antimicrobial susceptibility for both antibiotics and essential oil was determined by Kirby Bauer and broth dilution methods. Eleven male mice were used in the in vivo study, and each animal had wound infection on the dorsal inter-scapular skin region created with a 6 mm biopsy punch and 50 μl (adjusted to 0.5 McFarland standard) of MRSA. The size of the wound and its histological characteristics were used to estimate healing rate. Results The GC–MS investigation of the essential oil revealed six compounds, with benzene (2-nitroethyl) being the most prominent. Out of the eighteen (18) isolates examined, 12 MRSA strains were identified using the three methods for methicillin resistance determination, with about 80% of them being classified as biofilm producers. More than 60% of the MRSA isolates were resistant to erythromycin, fusidic acid, gentamicin and trimethoprim/sulfamethoxazole. The essential oil had greater antibacterial activity than the reference antibiotic, vancomycin. The essential oil had a minimum inhibitory concentration of 80 l/ml and a minimum bactericidal concentration of 160 l/ml (v/v). Haematoxylin and eosin staining revealed that the skin tissue that had been exposed to D. tripetala essential oil had a thicker epithelial layer, numerous fibroblasts, a build-up of collagen, and many blood cells. Conclusions The results showed that D. tripetala essential oil has powerful anti-staphylococcal properties as well as the capacity to expedite wound healing. This suggests that D. tripetala essential oil could be a successful candidate for developing a topical agent for wound management.